文章：

黑色素瘤中的BRAF突变：生物学特征、治疗意义及循环生物标志物

BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers

原文发布日期：8 August 2023

DOI: 10.3390/cancers15164026

类型: Review

开放获取: 是

英文摘要：

Melanoma is an aggressive form of skin cancer resulting from the malignant transformation of melanocytes. Recent therapeutic approaches, including targeted therapy and immunotherapy, have improved the prognosis and outcome of melanoma patients. BRAF is one of the most frequently mutated oncogenes recognised in melanoma. The most frequent oncogenic BRAF mutations consist of a single point mutation at codon 600 (mostly V600E) that leads to constitutive activation of the BRAF/MEK/ERK (MAPK) signalling pathway. Therefore, mutated BRAF has become a useful target for molecular therapy and the use of BRAF kinase inhibitors has shown promising results. However, several resistance mechanisms invariably develop leading to therapeutic failure. The aim of this manuscript is to review the role of BRAF mutational status in the pathogenesis of melanoma and its impact on differentiation and inflammation. Moreover, this review focuses on the mechanisms responsible for resistance to targeted therapies in BRAF-mutated melanoma and provides an overview of circulating biomarkers including circulating tumour cells, circulating tumour DNA, and non-coding RNAs.

摘要翻译： 

黑色素瘤是一种由黑色素细胞恶性转化形成的侵袭性皮肤癌。近年来，靶向治疗和免疫治疗等新方法改善了患者的预后。BRAF基因是黑色素瘤中最常发生突变的致癌基因之一，其最常见的突变形式为第600密码子的单点突变（主要为V600E），该突变导致BRAF/MEK/ERK（MAPK）信号通路持续性激活。因此，突变的BRAF已成为分子治疗的重要靶点，BRAF激酶抑制剂的应用已显示出良好疗效。然而，多种耐药机制的出现常导致治疗失败。本文旨在综述BRAF突变状态在黑色素瘤发病机制中的作用及其对细胞分化与炎症过程的影响，并重点探讨BRAF突变型黑色素瘤对靶向治疗产生耐药性的机制，同时概述循环肿瘤细胞、循环肿瘤DNA及非编码RNA等循环生物标志物的研究进展。

原文链接：

BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers